Synergistic increases in IL-1 synthesis by the human monocytic cell line THP-1 treated with PAF and endotoxin.
The capacity to stimulate cytokine release may be important to the long-term effects of platelet-activating factor (PAF), which has a very short half-life. Previous studies have shown that PAF stimulates interleukin 1 (IL-1) release by human monocytes. IL-1 and other cytokines produced in response to PAF may be important to the long-term effects of this short-lived lipid. The THP-1 human monocytic leukemia cell line, was used to study the mechanism by which PAF stimulates IL-1 release. PAF stimulates the release of IL-1 beta activity into THP-1 cell supernatants with a multiphasic dose-response curve very similar to that for monocytes. When THP-1 cells are treated with PAF and LPS in combination, these two stimuli interact synergistically to greatly increase the release of IL-1 activity. To assess the effect of PAF on IL-1 beta synthesis, THP-1 cell pellet proteins were separated by SDS-PAGE, blotted, and immunostained to detect IL-1 beta. Immunostaining revealed that PAF increases intracellular IL-1 beta precursor and that the combination of PAF and LPS increases IL-1 beta precursor synergistically. PAF increases IL-1 beta release mainly by increasing IL-1 beta synthesis.
Barthelson
R A
RA
Department of Medicine, Veterans Administration Medical Center, San Francisco, California 94121.
Potter
T
T
Valone
F H
FH
D015153:Blotting, Western; D002460:Cell Line; D015232:Dinoprostone / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004731:Endotoxins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis*; D008070:Lipopolysaccharides / Q000494:pharmacology; D009000:Monocytes / Q000378:metabolism*; D010972:Platelet Activating Factor / Q000494:pharmacology*
D004731:Endotoxins; D007375:Interleukin-1; D008070:Lipopolysaccharides; D010972:Platelet Activating Factor; D015232:Dinoprostone